Validation microbiological

All disinfection and sterilization processes for equipment should be validated, for preference using a microbiological challenge with an organism of appropriate resistance to the disinfectant, sterilant or sterilizing conditions. Once the required log reduction of the challenge organism has been achieved, physical and/or chemical parameters can be set which form the critical control points for the process. 

There is an apparent anomaly in that it also states that the preferred combination of temperature and time is a minimum of 121 °C maintained for 15 minutes, which, by definition, equates to an Fq value of 15. The latter, however, is applicable where the material to be sterilized may contain relatively large numbers of thermophilic bacterial spores, and an Fq of 8 is appropriate for a microbiologically validated process where the bioburden is low and the spores likely to be present are those of (the generally more heat sensitive) mesophilic species. 

The QPP has three laboratories the Environmental Chemistry Laboratory (ECL) in Bay St. Louis, MS, and the Analytical Chemistry Laboratory (ACL) and the Microbiology Laboratory at the Environmental Science Center, both at Fort Meade, MD. The ECL is heavily involved with method validation efforts. The ACL evaluates enforcement analytical methods for product chemistry to ensure that the ingredient statements on the label are accurate and evaluates residue analytical methods for... 

Microbiological aspects will need to be discussed, but the amount of information will depend on the type of product. For nonsterile products there will need to be a description of the microbiological attributes of the product and, if appropriate, a rationale for not performing microbial limit tests. For preserved products the selection of the antimicrobial preservatives will need to be discussed and the effectiveness of the selected system demonstrated. For sterile products there will need to be appropriate process validation data and information on the integrity of the container-closure system. 

Appropriate procedures, designed to prevent microbiological contamination of compounded drug products purporting to be sterile, shall be established and followed. Such procedures shall include validation of any sterilization process. 

According to 211.113 Control of microbiological contamination, pharmaceutical manufacturers need written procedures describing the systems designed to prevent objectionable microorganisms in both nonsterile and sterile drug products. All sterilization processes used to manufacture parenteral drugs need to be validated. 

USP 24 Testing Chapters (51) Antimicrobial Effectiveness Testing, (61) Microbial Limit Tests and (71) Sterility Tests, United States Pharmacopeial Convention, Inc., Rockville, MD, 2000. USP 24 Informational Chapters (1116) Microbiological Evaluation of Clean Rooms and other Controlled Environments, (1111) Microbiological Attributes of Pharmaceutical Articles, (1151) Pharmaceutical Dosage Forms, (1225) Validation of Compendial Methods, and (1231) Water for Pharmaceutical Purposes, United States Pharmacopeial Convention, Inc., Rockville, MD, 2000. 

PDA Technical ReportNo. 33, The Evaluation, Validation and Implementation of New Microbiological Testing Methods, Bethesda, MD, June 2000. 

Van Leeuwen W., H. Verbmgh, J. van der Velden, N. van Leeuwen, M. Heck, and A. van Belkum (1999). Validation of binary typing for Staphylococcus aureus strains. Journal of Clinical Microbiology 37 664-674. 

The modified ITT, where unqualified patients are excluded, and patients with clinically and or microbiologically documented infections (as stated in the protocol), who have received at least one dose of the investigated drug thus addressed, is particularly valid for regulatory purposes. ... 

In the case of recombinant proteins intended for use in sterile pharmaceutical products, additional process controls on microbiologic aspects of analysis must be established and validated to ensure aseptic conditions throughout the manufacturing process. 

Supported by the overall development in all fields of analysis during the past few decades, a precise analytical methodology has been developed for the different aspects of quality control, comprising physicochemical, biotechnological, sensory and microbiological methods. In order to meet the sense of the quality control system and by that the customers requirements, all methods applied have to be validated by adequate quality assurance tools. 

To describe the procedure for validation of an ampule and vial washing machine to maintain microbiological quality... 

To provide the guideline for validation of the microbiological methods to ensure analytical accuracy and precision and that the methods are suitable for the intended use... 

The main objective of validation of an analytical procedure is to demonstrate that the procedure is suitable for its intended purpose. The procedures presented in this SOP provide basic guidelines for the validation of methods for microbiological assay, estimation of the number of microorganisms, detection of indicators of objectionable microorganisms, validation of preservative efficacy testing, and validation of the sterility testing and endotoxin test (LAL test). 

It is an essential condition of biological assay methods that the tests on the standard preparation and on the sample whose potency is being determined should be carried out at the same time and, in all other respects, under strictly comparable conditions. The validation of microbiological assay method includes performance criteria (analytical parameters) such as linearity, range, accuracy, precision, specificity, etc. 

Requirements for hold time limits and protection of product microbiological quality are described in manufacturing site SOPs. The hold times for (product name) USP will be validated during manufacturing of process validation lots. 

The heating regimen is developed using a KAYE validator or equivalent and copper-constantan thermocouples. The determination of the load cold spot is achieved by actual experiments. A microbiological challenge test was performed to verify the sterilization conditions. Biological indicators... 

The method for sterility testing of (product name) USP is manufacturing site SOP and the microbiological sterility method validation summary report is provided in (provide reference attachment number). The USP bacteriostasis/fungistasis test was performed to validate the sterility test method... 

Sterility testing of (specify name) USP microbiological sterility method validation summary report... 

Perform microbiological challenge studies to determine the degree of process lethality provided by the sterilization cycle. The microorganisms most frequently utilized to challenge steam sterilizer cycles are Bacillus stearothermophilus and ATCC 7953. The Kaye validator equipped with 12 (minimum) thermocouples and biological indicators (10 ) shall be positioned in the detected cool points of the chamber and condenser. After the sterilization cycle is complete, the B.I s are recovered and subjected to microbiological test procedures. 

All microbiological isolation techniques used for the environmental monitoring shall be validated and, in addition, media shall be examined for sterility and for growth promotion as indicated next. 

MICROBIOLOGY VALIDATION REPORT STERILITY TEST OF (PRODUCT NAME) COMPLEMENTARY TEST... 

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